Heterocylic arseno-compounds and process of purifying same



Patented Mar. 21, 1933 TEJLS *umrrso STA PATENT OFFICE I ARTHUR BINZ, or BERLImAND com: aim, or RANGSDORF, GERMANY HE' IEROGYLIC ARSENO-GOMPOUNDS AND PROCESS OF PUBIF YI NGT'SAME I No Drawing; Original application filed No vember s, 1924, Serial no. 748,717, and in Germany November '19, 1923. Divided and.this application filed March 38, 1927. Serial N0.179,180. 1

Our invention relates to valuable heterocyclical compounds of arsenic and process of purifying same. According to our present invent-ion such compounds are obtained 5 by causing heterocyclical diazo compounds to react with solubleinorganic arsenites and converting the products-thus obtained into substances of a lower degree of'oxidation by treatment with a reducing agent.

For example, if amino derivatives of heterocyclical compounds capable of being diazotized, for instance amino derivatives of the pyridine or quinoli-ne series, are converted into diazo compounds and the other component of thereactiom'such as for instance an arsenious salt or free arsenious acid, is

allowed to act upon the said 'diazo compounds, there are obtained heterocyclical arsenic acids or the salts thereof described in 29' our'patent' of the United States No. 1,7 02,-

If such compounds are now treated with reducing agents, they are converted} into compounds of a lower degree of oxidation, for instance into arsine oxides and the like or into the corresponding arseno compounds.

As starting materials for the preparation of compounds in accordance with the present invention substances with heterocyclical 3 nuclei of various kinds may be used, for example such which contain nitrogen or oxygen or sulfur or sulfur dioxide, or elements or groups of diiferent kinds, for example nitrogen and sulfur. The starting materials can be substituted, the substituting radicle being advantageously of an electronegative" nature or having a therapeutical influence. Such substituents are" for-"example groups such as the hydroxyl group, amino group, acetyl amino. gr'oup,.glycine group or halogen forinstance chlorine etc. materials containing several substituents can be used for carrying out our invention. In-

stead of starting from substituted com-Q.

pounds the present invention can alsobe carried into effect in certain cases by first llltIOdIlClIlgthG arsonicacid radicle or other radicles of the kind by the agency of the diazo process and afterwards the desired substituents. I

Starting The introduction of *arsenic can be achieved in neutral, acid or alkaline-solution at ordinary or elevated temperature. It is advisable to previously-ascertain by experie 7 ment. the method best suited; for the process: i

The reaction can be carried outby employ-i;

ing equimolecular quantities of the reacting compounds. Generally, however,"it*is more favorable to use an excess, which in certain cases may even be fairlyzlarga -of the arsenic compound, for example o'nemoleculei of the heterocyclicahstarting .material to 2 3 molecules and even more of alkali ar-' 'senite. In some casesthe reaction is advanerocyclical arseno compoundsiofthe type RAs ='AsR can beobtained by starting from oxides, for instance arsine oxides of thetype RAs=O and treating themwith reducing agents. 7 c 7 By converting arsenic acids or the like into arseno compoundsit s possible to easily purify the former'eubstances. Thus, the

heterocyclical arsonicacids, prepared according to our'invention through the agency of. the diazo process or by any other method, areconverted into the corresponding arseno compounds by treatingthem'with reducing;- agents, whereafter the latter are reconverted into the corresponding acids by the-treatment with suitable oxidizing agents, forinstance hydrogen peroxide. 2 V 1 v I g Edamplel' V i H Onev molecular weight of 2-hydr0xy-5am1 ino pyridine is diazoti'z ed in hydrochloric acid solution in the usual way by adding f 7 sodium nitrite. The diazo solution thus obtained is added drop by drop to a solution, of g sodium arseniter The liquid, made slightly alkaline, is then allowed to stand for some time to complete the reaction. The 2-hydr0xy-5-pyridine' arsenic acid: is ob: tained from the solution in the "way cus-l tomary for the" preparation. of aromatic 9 arsonic acids; The arsonic acid obtained according. to this prescription is treated with hypophosphorous acid, preferably out of contact with air whilst heating moderateeddrop by drop to a' solution containing an ,quinoline-arsonic acid is obtained.

ly. After some time the 2, 25, 5'-dihy droxy-di-arsenopyridine separates as a light yellow powder which is sparingly soluble in the usual solvents.

' As As HO U011 N s N Bytreating-this substance with dilute hydrogen peroxide of about 3% in the cold the acid is again obtained, from which we started, but freefrom impurities.

Example 2 30 grams of ana-amino-quinoline are dissolved in 300 ccbof water and 120 cc. of

concentrated hydrochloric acid and the solution is mixed with 15 grams of sodium nitrite in 200 cc. of water. To the acid diazoniumsolution alkali is added until the acid reaction towards congo reagent paper has disappeared. The solution is then addexcess of-isodium arsenite. After stirring for one hour the solution is filtered, concentrated to about 500 cc. acidulated with I hydrochloric acid and then, by treatment with sodium hypohosphite, the arseno compound is separated. I By treating the arseno derivative with hydrogen peroxide the ana- It is readilysoluble in Water, acids and alkalies. From highly diluted hydrochloric acid the hydrochloride ofthe acid crystallizes with one molecule of water of crystallization.

HzOaAs Z] nctmo \N I E sample 3 I 5. grams of the pure ana -q'uinoline-arsonic acid are dissolved in dilute hydrochloric acid and about 15 grams of; sodium hypozphosphite are added. The mixture is then warmed on a water bath for some time. orange preclpltate is formed which is fil tered off and washed with dilute hydrochloric acid. The ana-arseno-quinoline hydrochloride is-readily soluble in water.

' Example];

Q30 gramsof 6-amino-quinoline are diazotized in the'way described in Example 2.

. The resulting diazonium solution is added As i l q .2130] N/ 7 boiled with animal charcoal. After some 7 time the arsonic acid crystallizes out and is for purifying purposes recrystallized from water. grams 'oft-quinoline-ar'sonic acid thus obtained are dissolved in dilute hydrochloric acid and grams of sodium hypophosphite are added. The mixture is then heated for some time on the Water bath. The orange precipitate formed is filtered off and washed with water. The

resulting fi-arsenoquino-line hydrochloride is insoluble in Water, soluble chloric acid grams of 8-amino-quinoline are diazotiz'ed and arsenized in accordance with Exin strong hydro- Example 5 V As'v @N 2m p amples 2 and 4. From the resulting solution the arsonic acid is isolated bymeans of the oxidizing methOddeSCribed in Example 4. The S-quinoline-arsonic acid obtained in this way is sparingly soluble in water, readily soluble in acids, caustic alkalies and soda carbonate. 5 grams of S-quinOline-arsonic acid are dissolved in dilute hydrochloric acid and reduced with the aid of 15 grams of sodium hypophosphite. The 8-arsenoquinoline-dihydrochlorideis insoluble in water, soluble in strong hydrochloric acid.

I Example 6 10 grams of S-quinoline-arsonic acid are dissolved in 150 cc. of water and 3.2 grams of caustic soda. A solution of 2.5 grams of potassium iodide and 10 grams of concentrated sulfuric acid in 50 cc. of water are added. Thereupon sulfurous acid is passed into the mixture during about 6' hours the temperature not exceeding 10 C. The mixture is boiled whilst stirring vigorously, well cooled,f-made strongly alkaline by the addition of ammonia and filtered after standing for severalhoursf The residue is washed with water. For purification purposes the crude product is dissolved,'when still moist, in 50 cc. of water and 45cc. of

2 N-caustic soda solution, shaken severaltimes with ether, filtered and mixed with 50 cc. of 5-N-ammonium chloride solution.

The fiocculent precipitate which separates,

is filtered after it has been standing .for

several hours, washed with water and dried V sparingly soluble in acids, soluble in caustic soda.

As0 N In the same or a similar fashion as pyridine arsonic acids and quinoline arsonic acids a whole series of other heterocyclical arsonic acids can be prepared according to our invention, for example diphenyl-sulfonarsonic-acid, diphenyl-hydroxy-arsonic acid, indigotine-diarsonic acid, triazolearsonic acid, coumarone-arsonic acid,'carbazo1e arsonic acid, diphenyl-arsine-arsonic acid.

Various changes may be made in the details disclosed in the foregoing specification without departing from the invention or sacrificing the advantages thereof.

We claim 1. Process of purifying heterocyclical compounds which comprises transforming a heterocyclical compound of the arsonic acid type into a compound of a lower degree of oxidation by treating same with a reducing agent separating the resulting arseno compound by filtration and reconverting this arseno compound into the starting product by means of an oxidizing agent.

2. Process of purifying heterocyclical compounds which comprises treating a diazotized heterocyclical compound with a soluble inorganic arsenite, reducing the compound of the arsonic acid type obtained separating the resulting arseno compoud byfiltration, reconverting this arseno compound into the arsonic acid by oxidation and converting such acid into its salt.

3. Process of manufacturing heterocyclical compounds which comprises causing a soluble inorganic arsenite to react with a pyridine diazo compound and converting the product thus obtained into a substance probably the formula U U I no on N N V In testimony whereof We aflix our signatures.

ARTHUI; BINZ. GURT BATH. 

